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Abstract: Acute intoxication with organophosphorus (OP) cholinesterase inhibitors can produce seizures that rapidly progress to life-threateningstatus epilepticus. Significant research effort has been invested investigating the involvement of muscarinic acetylcholine receptors (mAChRs) in OP-induced seizure activity. In contrast, there has been far less effort focused on nicotinic AChRs (nAChRs) in this context. Here, we address this data gap using a combination ofin vitroandin vivomodels. Pharmacological antagonism and genetic deletion of α4, but not α7, nAChR subunits prevented or significantly attenuated OP-induced electrical spike activity in acute hippocampal slices and seizure activity in mice, indicating that α4 nAChR activation is necessary for neuronal hyperexcitability triggered by acute OP exposures. These findings not only suggest that therapeutic strategies for inhibiting the α4 nAChR subunit warrant further investigation as prophylactic and acute treatments for acute OP-induced seizures, but also provide mechanistic insight into the role of the nicotinic cholinergic system in seizure generation.

Stem cells exist in vitro in a spectrum of interconvertible pluripotent states. Analyzing hundreds of hiPSCs derived from different individuals, we show the proportions of these pluripotent states vary considerably across lines. We discover 13 gene network modules (GNMs) and 13 regulatory network modules (RNMs), which are highly correlated with each other suggesting that the coordinated co-accessibility of regulatory elements in the RNMs likely underlie the coordinated expression of genes in the GNMs. Epigenetic analyses reveal that regulatory networks underlying self-renewal and pluripotency are more complex than previously realized. Genetic analyses identify thousands of regulatory variants that overlapped predicted transcription factor binding sites and are associated with chromatin accessibility in the hiPSCs. We show that the master regulator of pluripotency, the NANOG-OCT4 Complex, and its associated network are significantly enriched for regulatory variants with large effects, suggesting that they play a role in the varying cellular proportions of pluripotency states between hiPSCs. Our work bins tens of thousands of regulatory elements in hiPSCs into discrete regulatory networks, shows that pluripotency and self-renewal processes have a surprising level of regulatory complexity, and suggests that genetic factors may contribute to cell state transitions in human iPSC lines.

The inner ear is the hub where hair cells (HCs) transduce sound, gravity, and head acceleration stimuli to the brain. Hearing and balance rely on mechanosensation, the fastest sensory signals transmitted to the brain. The mechanoelectrical transducer (MET) channel is the entryway for the sound-balance-brain interface, but the channel-complex composition is not entirely known. Here, we report that the mouse utilizes Piezo1 (Pz1) and Piezo2 (Pz2) isoforms as MET-complex components. The Pz channels, expressed in HC stereocilia, and cell lines are co-localized and co-assembled with MET complex partners. Mice expressing non-functional Pz1 and Pz2 at the ROSA26 locus have impaired auditory and vestibular traits that can only be explained if the Pzs are integral to the MET complex. We suggest that Pz subunits constitute part of the MET complex and that interactions with other MET complex components yield functional MET units to generate HC MET currents.

Some theories have proposed that autistic individuals have difficulty learning predictive relationships. We tested this hypothesis using a serial reaction time task in which participants learned to predict the locations of a repeating sequence of target locations. We conducted a large-sample online study with 61 autistic and 71 neurotypical adults. The autistic group had slower overall reaction times, but demonstrated sequence-specific learning equivalent to the neurotypical group, consistent with other findings of typical procedural memory in autism. The neurotypical group, however, made significantly more prediction-related errors early in the experiment when the stimuli changed from repeated sequences to random locations, suggesting certain limited behavioural differences in the learning or utilization of predictive relationships for autistic adults.

Abstract Stem cells exist in vitro in a spectrum of interconvertible pluripotent states. Analyzing hundreds of hiPSCs derived from different individuals, we show the proportions of these pluripotent states vary considerably across lines. We discover 13 gene network modules (GNMs) and 13 regulatory network modules (RNMs), which are highly correlated with each other suggesting that the coordinated co-accessibility of regulatory elements in the RNMs likely underlie the coordinated expression of genes in the GNMs. Epigenetic analyses reveal that regulatory networks underlying self-renewal and pluripotency are more complex than previously realized. Genetic analyses identify thousands of regulatory variants that overlapped predicted transcription factor binding sites and are associated with chromatin accessibility in the hiPSCs. We show that the master regulator of pluripotency, the NANOG-OCT4 Complex, and its associated network are significantly enriched for regulatory variants with large effects, suggesting that they play a role in the varying cellular proportions of pluripotency states between hiPSCs. Our work bins tens of thousands of regulatory elements in hiPSCs into discrete regulatory networks, shows that pluripotency and self-renewal processes have a surprising level of regulatory complexity, and suggests that genetic factors may contribute to cell state transitions in human iPSC lines.

Abstract The inner ear is the hub where hair cells (HCs) transduce sound, gravity, and head acceleration stimuli to the brain. Hearing and balance rely on mechanosensation, the fastest sensory signals transmitted to the brain. The mechanoelectrical transducer (MET) channel is the entryway for the sound-balance-brain interface, but the channel-complex composition is not entirely known. Here, we report that the mouse utilizes Piezo1 (Pz1) and Piezo2 (Pz2) isoforms as MET-complex components. The Pz channels, expressed in HC stereocilia, and cell lines are co-localized and co-assembled with MET complex partners. Mice expressing non-functional Pz1 and Pz2 at the ROSA26 locus have impaired auditory and vestibular traits that can only be explained if the Pzs are integral to the MET complex. We suggest that Pz subunits constitute part of the MET complex and that interactions with other MET complex components yield functional MET units to generate HC MET currents.

In this paper, we experimentally illustrate the effectiveness of neural networks (NNs) as non-linear equalisers for multilevel pulse amplitude modulation (PAM-M) transmission over an optical wireless communication (OWC) link. In our study, we compare the bit-error-rate (BER) performances of two decision feedback equalisers (DFEs)—a multilayer-perceptron-based DFE (MLPDFE), which is the NN equaliser, and a transversal DFE (TRDFE)—under two degrees of non-linear distortion using an eye-safe 850 nm single-mode vertical-cavity surface-emitting laser (SM-VCSEL). Our results consistently show that the MLPDFE delivers superior performance in comparison to the TRDFE, particularly in scenarios involving high non-linear distortion and PAM constellations with eight or more levels. At a forward error correction (FEC) threshold BER of 0.0038, we achieve bit rates of ~28 Gbps, ~29 Gbps, ~22.5 Gbps, and ~5 Gbps using PAM schemes with 2, 4, 8, and 16 levels, respectively, with the MLPDFE. Comparably, the TRDFE yields bit rates of ~28 Gbps and ~29 Gbps with PAM-2 and PAM-4, respectively. Higher PAM levels with the TRDFE result in BERs greater than 0.0038 for bit rates above 2 Gbps. These results highlight the effectiveness of the MLPDFE in optimising the performance of SM-VCSEL-based OWC systems across different modulation schemes and non-linear distortion levels.

Influenza A virus (IAV) is a common respiratory pathogen and a global cause of significant and often severe morbidity. Although inflammatory immune responses to IAV infections are well described, little is known about how neuroimmune processes contribute to IAV pathogenesis. In the present study, we employed surgical, genetic, and pharmacological approaches to manipulate pulmonary vagal sensory neuron innervation and activity in the lungs to explore potential crosstalk between pulmonary sensory neurons and immune processes. Intranasal inoculation of mice with H1N1 strains of IAV resulted in stereotypical antiviral lung inflammation and tissue pathology, changes in breathing, loss of body weight and other clinical signs of severe IAV disease. Unilateral cervical vagotomy and genetic ablation of pulmonary vagal sensory neurons had a moderate effect on the pulmonary inflammation induced by IAV infection, but significantly worsened clinical disease presentation. Inhibition of pulmonary vagal sensory neuron activity via inhalation of the charged sodium channel blocker, QX-314, resulted in a moderate decrease in lung pathology, but again this was accompanied by a paradoxical worsening of clinical signs. Notably, vagal sensory ganglia neuroinflammation was induced by IAV infection and this was significantly potentiated by QX-314 administration. This vagal ganglia hyperinflammation was characterized by alterations in IAV-induced host defense gene expression, increased neuropeptide gene and protein expression, and an increase in the number of inflammatory cells present within the ganglia. These data suggest that pulmonary vagal sensory neurons play a role in the regulation of the inflammatory process during IAV infection and suggest that vagal neuroinflammation may be an important contributor to IAV pathogenesis and clinical presentation. Targeting these pathways could offer therapeutic opportunities to treat IAV-induced morbidity and mortality.

Acute intoxication with organophosphorus (OP) cholinesterase inhibitors can produce seizures that rapidly progress to life-threatening status epilepticus. Significant research effort has been focused on investigating the involvement of muscarinic acetylcholine receptors (mAChRs) in OP-induced seizure activity. In contrast, there has been far less attention on nicotinic AChRs (nAChRs) in this context. Here, we address this data gap using a combination of in vitro and in vivo models. Pharmacological antagonism and genetic deletion of α4, but not α7, nAChR subunits prevented or significantly attenuated OP-induced electrical spike activity in acute hippocampal slices and seizure activity in mice, indicating that α4 nAChR activation is necessary for neuronal hyperexcitability triggered by acute OP exposures. These findings not only suggest that therapeutic strategies for inhibiting the α4 nAChR subunit warrant further investigation as prophylactic and immediate treatments for acute OP-induced seizures, but also provide mechanistic insight into the role of the nicotinic cholinergic system in seizure generation.

Underpinned by the human capital theory of migration, this study examines the drivers of unemployment duration in Ghana with a special focus on migration and education. This study employs semiparametric Cox regression and Cox proportional hazard models. Using a sample of 575 individuals in eight districts in Ghana, the study concludes that age, locality, social networks, alternative income sources, migration and education are significant factors influencing individual‐specific unemployment duration in Ghana. Also, the joint effect of education and migration status reduces unemployment duration. The study encourages the youth to take up voluntary services and other forms of industry attachments to build labour market experience. Again, the Ministry of Employment and Labour Relations should develop and implement industrial attachment and internship programmes as well as create equal job opportunities in rural areas to prevent rural–urban migration. [ABSTRACT FROM AUTHOR]

In this paper, we experimentally illustrate the effectiveness of neural networks (NNs) as non-linear equalisers for multilevel pulse amplitude modulation (PAM-M) transmission over an optical wireless communication (OWC) link. In our study, we compare the bit-error-rate (BER) performances of two decision feedback equalisers (DFEs)—a multilayer-perceptron-based DFE (MLPDFE), which is the NN equaliser, and a transversal DFE (TRDFE)—under two degrees of non-linear distortion using an eye-safe 850 nm single-mode vertical-cavity surface-emitting laser (SM-VCSEL). Our results consistently show that the MLPDFE delivers superior performance in comparison to the TRDFE, particularly in scenarios involving high non-linear distortion and PAM constellations with eight or more levels. At a forward error correction (FEC) threshold BER of 0.0038, we achieve bit rates of ~28 Gbps, ~29 Gbps, ~22.5 Gbps, and ~5 Gbps using PAM schemes with 2, 4, 8, and 16 levels, respectively, with the MLPDFE. Comparably, the TRDFE yields bit rates of ~28 Gbps and ~29 Gbps with PAM-2 and PAM-4, respectively. Higher PAM levels with the TRDFE result in BERs greater than 0.0038 for bit rates above 2 Gbps. These results highlight the effectiveness of the MLPDFE in optimising the performance of SM-VCSEL-based OWC systems across different modulation schemes and non-linear distortion levels. [ABSTRACT FROM AUTHOR]

This review examines the relationship between the crystallite size of cobalt and the distribution of products produced by Fischer-Tropsch synthesis (FTS). The ideal range for the average cobalt crystallite diameter is between 6 and 8 nm. Deviating from this range, whether by increasing or decreasing the crystallite size, influences the carbon monoxide (CO) turnover frequency and the selectivity of CH4, C2-C4, and C5+. To ensure the development of a consistent catalyst, careful monitoring and adjustment of the morphology, particle size, and metal loading on the support particles are essential. For experimental repeatability during FTS applications, it would be ideal if catalyst particles had crystallites of a uniform size. Methods for crystallite characterization and catalyst synthesis were also addressed in detail. The diameter of the cobalt crystallite appears to be a crucial parameter that influences cobalt oxidation, the thermodynamics of cobalt reduction and oxidation are reported. Conducting a Design of Experiment (DOE) with Design Experts on available literature led to determining optimal conditions for enhancing the primary target product of FTS—C5+ selectivity. [ABSTRACT FROM AUTHOR]

The United States is facing a mental health workforce shortage, exacerbated by the COVID-19 pandemic. Low- and middle-income countries (LMICs) have historically grappled with even greater shortages. Therefore, LMICs have thought creatively about expanding the mental health workforce and the settings in which to deliver evidence-based and equitable mental health care. The authors introduce some mental health interventions in LMICs, describe evidence of the efficacy of these interventions gleaned from this context, and discuss the applicability of these interventions to the United States. The authors also reflect on the benefits and challenges of implementing these interventions in the U.S. mental health care system to alleviate its current workforce shortage. [ABSTRACT FROM AUTHOR]

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The study demonstrates a new method to create high‐purity mesoporous silica from coal fly ash without using structure‐directing agents. Divided into two stages, the process involves pre‐treating the ash with Na2CO3, calcination, cooling, washing, and drying to yield a dehydrated sample. Subsequently, silica synthesis occurs through an acid refluxing technique using thermally activated coal fly ash with Na2CO3. Key factors impacting synthesis include acid content and liquid‐to‐solid ratio. The study extensively employs various characterization methods like XRF, XRD, FTIR, and BET analysis, revealing a 99.1 % purity in silica content, a surface area of 793.51 m2/g, and a pore size of 3.9 nm. Optimal conditions for this synthesis involve 80 °C temperature, 2‐hour reaction time, 25 % hydrochloric acid concentration, and a 10 : 1 liquid‐to‐solid ratio. FTIR spectra demonstrate similarities between the obtained silica and commercial Sigma Aldrich silica. This innovative approach presents a promising avenue for generating top‐quality silica from coal fly ash, potentially diversifying applications across industries reliant on high‐performance silica materials. [ABSTRACT FROM AUTHOR]

Neurofeedback concurrent with mindfulness meditation may reveal meditation effects on the brain and facilitate improved mental health outcomes. Here, we systematically reviewed EEG and fMRI studies of mindfulness meditation with neurofeedback (mbNF) and followed PRISMA guidelines. We identified 10 fMRI reports, consisting of 177 unique participants, and 9 EEG reports, consisting of 242 participants. Studies of fMRI focused primarily on downregulating the default-mode network (DMN). Although studies found decreases in DMN activations during neurofeedback, there is a lack of evidence for transfer effects, and the majority of studies did not employ adequate controls, e.g. sham neurofeedback. Accordingly, DMN decreases may have been confounded by general task-related deactivation. EEG studies typically examined alpha, gamma, and theta frequency bands, with the most robust evidence supporting the modulation of theta band activity. Both EEG and fMRI mbNF have been implemented with high fidelity in clinical populations. However, the mental health benefits of mbNF have not been established. In general, mbNF studies would benefit from sham-controlled RCTs, as well as clear reporting (e.g. CRED-NF)., Competing Interests: Declaration of Competing Interests: No competing interests are present.

As a major setback to the global coconut industry, lethal yellowing disease (LYD), caused by phytoplasmas, continues to threaten coconut palms in the Americas, the Caribbean, Africa, and Oceania. Despite its economic impacts, limited information exists on LYD vectors, which impedes the prevention and management of the disease. Using double-sided yellow sticky traps, we investigate the factors that influence the seasonal abundance and population dynamics of three sap-sucking insects of LYD, i.e., Diostrombus (Hemiptera: Derbidae) sp. and Patara sp. (Hemiptera: Derbidae), and Nedoptepa curta Dmitriev (Hemiptera: Cicadellidae), on five coconut genotypes (Sri Lanka Green Dwarf (SGD), Vanuatu Tall (VTT), SGD × VTT, Malayan Yellow Dwarf (MYD) × VTT, and West African Tall (WAT)) in the Western Region, and one (SGD) in the Central Region of Ghana from April 2019 to May 2021. The results showed that N. curta and Patara sp. were the most abundant species in the Western and Central Regions, respectively. There was a significant difference between the coconut cultivars and sap-sucking insects. The peak population development of the sap-sucking insects was recorded during the dry season on all the coconut genotypes at all sampling locations. A significant positive correlation was detected between temperature and the population of N. curta and Patara sp. In the Agona Nkwanta, VTT had the highest population of N. curta, whereas WAT had the highest population of Patara sp. and Diostrombus sp. These findings provide useful information for assessing the role of factors that could affect the Cape Saint Paul Wilt disease pathosystem., (© The Author(s) 2024. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Acute hyperglycemia or stress hyperglycemia is a frequent finding in patients with acute coronary syndrome (ACS). Several studies have demonstrated the association between acute hyperglycemia with short- and long-term mortality in ACS patients. But the evidence is not concrete. We gathered 1056 articles from three databases, i.e., PubMed, Google Scholar, and Science Direct using different search strategies and filters. We then removed duplicates and 919 articles were screened with title abstract and full text. After a full-text screening of 169 articles, we removed 116 articles. We then applied eligibility criteria and did a quality assessment of articles and finally, we included 21 articles in our study. The 21 articles spanned years 2014 to 2024. Of them, 16 articles were observational studies, two were systematic reviews and meta-analyses, and three were review articles. Six articles used stress hyperglycemia ratio (SHR) alone, seven articles used admission blood glucose (ABG) alone, two used fasting plasma glucose (FPG) alone and one used SHR, ABG, and FPG together as a parameter to measure acute hyperglycemia. Short-term poor outcomes (in-hospital, <30 days) were studied in 12 studies, and long-term poor outcomes (>30 days-1 year, >1 year) were studied in six studies. A positive correlation between acute hyperglycemia and short- and long-term mortality was found in our 21 included studies. The three parameters which are used to quantify acute or stress hyperglycemia in our study, i.e., SHR, ABG, and FPG predict both short- and long-term mortality in ACS patients. Further study is needed to determine the accurate cutoff level of hyperglycemia to be called acute hyperglycemia in diabetics. We tried to review the recent literature on this topic to deepen our understanding of this topic and to provide a base for future research., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Pandey et al.)

Genetic variations among people mainly determine the blood levels of lipoprotein (a) (Lp(a)), and it is relatively stable throughout one's lifetime. Nevertheless, there could still be other factors that control the Lp(a) level. Thyroid hormones are known to influence the serum lipid level by regulating the expression of key enzymes that are involved in lipid metabolism. Both hypo and hyperthyroidism are associated with changes in lipid levels. Even though thyroid hormone abnormalities have been shown to alter traditional lipid parameters like low-density lipoprotein (LDL-C), its influence on Lp(a) has not been established. This review aims to identify the relationship between Lp(a) and thyroid hormones by reviewing data from correlative studies and observing treatment-related Lp(a) level changes in thyroid disorders from interventional studies. We searched MEDLINE, Cochrane, and Google Scholar databases with predefined search criteria and search strategies for paper identification. Individual reviewers reviewed identified papers for selection. Finalized papers were reviewed for Lp(a) levels and their responses to treatment in patients with thyroid disorders to establish the relationship between Lp(a) and thyroid hormone. We concluded that the data were limited and sometimes contradicted one another to establish a clear relationship between Lp(a) and thyroid hormones. Even though correlative studies data showed strong indications that overt-hypothyroidism was associated with high Lp(a) levels, thyroid hormone replacement studies did not show any significant changes in Lp(a) levels compared to pre-treatment in patients with both overt-hypothyroidism and subclinical hypothyroidism. More clinical trials focusing on Lp(a) with longer periods of treatment and follow-up in thyroid patients are needed to establish the relationship between the two. The possibility of dose-related Lp(a) responses to thyroid hormone treatment should also be explored., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Lwin et al.)